Suven Life Sciences Limited · NSE:SUVEN
Suven Life Sciences — 12th Clinical Trials on Alzheimer's Disease (CTAD) 2019
15 slides from Suven Life Sciences's conference presentation, December 2019
Slide 1: Masupirdine in Combination with Donepezil and Memantine in Moderate Alzheimer's: Phase 2 Outcomes
Masupirdine (SUVN-502), a 5-HT6 Receptor Antagonist in Combination with Donepezil and Memantine in Moderate Alzheimer's Patients: Study Outcomes from a Phase 2 Study Dr. Jeffrey Cummings, MD, ScD Department of Brain Health, School of Integrated Health Sciences, University of Nevada; Cleveland Clinic
Slide 2: Presenter Disclosures
Presenter Disclosures Dr. Cummings has provided consultation to Acadia, Actinogen, AgeneBio, Alkahest, Alzheon, Avanir, Axsome, Biogen, Cassava, Cerecin, Cerevel, Cognoptix, Cortexyme, EIP Pharma, Eisai, Foresight, Green Valley, Grifols, Hisun, Idorsia, Karuna, Nutricia, Orion, Otsuka, Probiodrug, Q
Slide 3: 5-HT6 Receptor: Cognition and Behavior
5-HT6 Receptor: Cognition and Behavior 5-HT6 receptor is a G-protein coupled receptor mediating its effects through cAMP pathways; Ca2+ signaling, and ERK1/2 pathway.1 Highest density of the receptor is found in cortex, dorsal hippocampus and striatum; brain areas primarily involved in cognition
Slide 4: Masupirdine: Overview
Masupirdine: Overview Non-clinical Masupirdine is a pure 5-HT6 receptor antagonist (>1200 fold selectivity over 5-HT2A receptor) Robust efficacy for cognition in animal models Elevates brain acetylcholine levels and neural oscillatory pattern of theta rhythm Attenuates aggressive behavior in
Slide 5: Phase 2 Proof of Concept Study Design
Masupirdine: Phase 2 Proof of Concept Study Design 5-HT6 receptor antagonist, Masupirdine in combination with Donepezil and Memantine (Triple Therapy) Screening Period: Treatment Period: Placebo Washout Endpoints Day -28 to Day -14 26 Weeks Period: 4 Weeks Randomization (1:1:1) • Moderate AD patient
Slide 6: Study Population and Demographics
Masupirdine: Study Population and Demographics Masupirdine Masupirdine Variables Placebo Total 50 mg 100 mg Study Population Randomized with intent to treat, n 188 187 183 558 Safety Population, n (%) 188 (100) 187 (100) 181 (98.9) 556 (99.6) Modified Intent to Treat, n (%) 183 (97.3) 184 (98.4) 176
Slide 7: Baseline Characteristics
Masupirdine: Baseline Characteristics Masupirdine Masupirdine Placebo Total Variables* 50 mg 100 mg n=183 n=184 n=176 n=543 ADAS-Cog 11, Mean (SD) 28.4 (8.2) 27.7 (6.9) 27.9 (8.6) 28.0 (7.9) MMSE, Mean (SD) 16.5 (2.5) 16.9 (2.2) 17.0 (2.5) 16.8 (2.4) Memantine Regimen Memantine IR 10 mg, BID, n (%)
Slide 8: Primary Outcome, ADAS-Cog
Masupirdine: Primary Outcome, ADAS-Cog 11 mITT EP 4 P la c e b o 4 P la c e b o M a s u p ir d in e 5 0 m g M a s u p ir d in e 5 0 m g 3 3 M e a n c h a n g e f r o m b a s e lin e M e a n c h a n g e f r o m b a s e lin e M a s u p ir d in e 1 0 0 m g M a s u p ir d in e 1 0 0 m g ∆ = - 0 .4 ∆ = -
Slide 9: Secondary Outcomes
Masupirdine: Secondary Outcomes - 1 .5 P la c e b o MMSE -6 P la c e b o ADCS-ADL 23 M a s u p ir d in e 5 0 m g M a s u p ir d in e 5 0 m g M e a n c h a n g e fr o m b a s e lin e M e a n c h a n g e fr o m b a s e lin e M a s u p ir d in e 1 0 0 m g M a s u p ir d in e 1 0 0 m g ∆ = - 0 .3 - 1 .0
Slide 10: Safety and Tolerability
Masupirdine: Safety and Tolerability Number (%) of Subjects Masupirdine Masupirdine Placebo Total 50 mg 100 mg Any TEAE 108 (57.4) 101 (54.0) 107 (59.1) 316 (56.8) Any Treatment Related AE 21 (11.2) 29 (15.5) 38 (21.0) 88 (15.8) Any Serious TEAE 12 (6.4) 10 (5.3) 14 (7.7) 36 (6.5) Any Treatment Rela
Slide 11: Hypothesis-Generating Subgroup Analyses: Cognition, ADAS-Cog 11
Hypothesis-Generating Subgroup Analyses Masupirdine: Effect on Cognition, ADAS-Cog 11 Memantine plasma concentrations ≤ 100 ng/mL Memantine use > 4 years 6 P la c e b o 10 P la c e b o M a s u p ir d in e 5 0 m g M a s u p ir d in e 5 0 m g M e a n c h a n g e f r o m b a s e lin e M e a n c h a n g
Slide 12: Hypothesis-Generating Subgroup Analyses: NPI Domains
Hypothesis-Generating Subgroup Analyses Masupirdine: Effect on NPI Domains Agitation/Aggression Delusions and Hallucinations 2 P la c e b o 3 P la c e b o M a s u p ir d in e 5 0 m g M a s u p ir d in e 5 0 m g M e a n c h a n g e f r o m b a s e lin e M e a n c h a n g e f r o m b a s e lin e 1 2 M
Slide 13: Summary and Conclusions
Masupirdine: Summary and Conclusions First trial where 5-HT6 antagonist was tested in combination with standard of care, donepezil and memantine. Masupirdine is safe and well tolerated. Masupirdine in combination with donepezil and memantine missed its primary endpoint. Hypothesis-generating
Slide 14: Acknowledgements
Acknowledgements Sponsor wishes to thank all subjects, their family members and investigators participated in this masupirdine phase 2 POC study. 14 Company Confidential Copyright © 2019 Suven Life Sciences Limited
Slide 15: Posters on Subgroup Analyses
Masupirdine: Posters on Subgroup Analyses Dec 4 - 5, 2019 P37: Subgroup analyses of memantine regimen, concentrations and duration of treatment P38: Potential benefits on Behavioral and Psychological Symptoms (BPSD) in patients with moderate Alzheimer's disease Dec 6 - 7, 2019 P180: Effect of AD dur
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